A1A1A_DANRE
ID A1A1A_DANRE Reviewed; 324 AA.
AC Q6AZW2; A2CE54;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Aldo-keto reductase family 1 member A1-A;
DE AltName: Full=Alcohol dehydrogenase [NADP(+)] A;
DE EC=1.1.1.2 {ECO:0000250|UniProtKB:P14550};
DE AltName: Full=Aldehyde reductase-A;
GN Name=akr1a1a; ORFNames=si:ch211-113n10.1, zgc:100940;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the NADPH-dependent reduction of a wide variety of
CC carbonyl-containing compounds to their corresponding alcohols. Displays
CC enzymatic activity towards endogenous metabolites such as aromatic and
CC aliphatic aldehydes, ketones, monosaccharides and bile acids. Acts as
CC an aldehyde-detoxification enzyme (By similarity). Displays no
CC reductase activity towards retinoids (By similarity).
CC {ECO:0000250|UniProtKB:P14550, ECO:0000250|UniProtKB:P50578,
CC ECO:0000250|UniProtKB:P51635}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a primary alcohol + NADP(+) = an aldehyde + H(+) + NADPH;
CC Xref=Rhea:RHEA:15937, ChEBI:CHEBI:15378, ChEBI:CHEBI:15734,
CC ChEBI:CHEBI:17478, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.2;
CC Evidence={ECO:0000250|UniProtKB:P14550};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9JII6}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q9JII6}.
CC -!- SIMILARITY: Belongs to the aldo/keto reductase family. {ECO:0000305}.
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DR EMBL; CR318632; CAM13142.1; -; Genomic_DNA.
DR EMBL; CR753867; CAM13142.1; JOINED; Genomic_DNA.
DR EMBL; CR753867; CAN88791.1; -; Genomic_DNA.
DR EMBL; CR318632; CAN88791.1; JOINED; Genomic_DNA.
DR EMBL; BC077140; AAH77140.1; -; mRNA.
DR RefSeq; NP_001003783.1; NM_001003783.2.
DR AlphaFoldDB; Q6AZW2; -.
DR SMR; Q6AZW2; -.
DR STRING; 7955.ENSDARP00000051081; -.
DR PaxDb; Q6AZW2; -.
DR Ensembl; ENSDART00000051082; ENSDARP00000051081; ENSDARG00000035257.
DR GeneID; 445326; -.
DR KEGG; dre:445326; -.
DR CTD; 445326; -.
DR ZFIN; ZDB-GENE-040808-44; akr1a1a.
DR eggNOG; KOG1577; Eukaryota.
DR GeneTree; ENSGT00940000166020; -.
DR InParanoid; Q6AZW2; -.
DR OMA; FMTMKAA; -.
DR OrthoDB; 1016440at2759; -.
DR PhylomeDB; Q6AZW2; -.
DR TreeFam; TF106492; -.
DR PRO; PR:Q6AZW2; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000035257; Expressed in intestine and 12 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0004032; F:alditol:NADP+ 1-oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0046185; P:aldehyde catabolic process; IEA:InterPro.
DR GO; GO:0110095; P:cellular detoxification of aldehyde; ISS:UniProtKB.
DR CDD; cd19106; AKR_AKR1A1-4; 1.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR020471; AKR.
DR InterPro; IPR044481; AKR1A.
DR InterPro; IPR018170; Aldo/ket_reductase_CS.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR PIRSF; PIRSF000097; AKR; 1.
DR PRINTS; PR00069; ALDKETRDTASE.
DR SUPFAM; SSF51430; SSF51430; 1.
DR PROSITE; PS00798; ALDOKETO_REDUCTASE_1; 1.
DR PROSITE; PS00062; ALDOKETO_REDUCTASE_2; 1.
DR PROSITE; PS00063; ALDOKETO_REDUCTASE_3; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasm; Membrane; NADP; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..324
FT /note="Aldo-keto reductase family 1 member A1-A"
FT /id="PRO_0000384152"
FT ACT_SITE 49
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT BINDING 112
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT BINDING 210..272
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250"
FT SITE 79
FT /note="Lowers pKa of active site Tyr"
FT /evidence="ECO:0000250|UniProtKB:P14550"
FT CONFLICT 196
FT /note="V -> A (in Ref. 2; AAH77140)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="I -> V (in Ref. 2; AAH77140)"
FT /evidence="ECO:0000305"
FT CONFLICT 314
FT /note="K -> N (in Ref. 2; AAH77140)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 324 AA; 36762 MW; 74BAFFE5775EE624 CRC64;
MTATITLSTG QRMPTVGLGT WKSAPGQVKQ AVLAALDCGY RHIDCAAAYS NEREVGEALT
ERLGPGKSLR RDDIFVTSKL WNTKHHPDDV EEACRRSLSD LRLSYLDLYL IHWPMAFGRG
DELIPRHPDG TIQYDDTHYR DTWAAMEKLV DQGLAKAIGL SNFNAKQIDD ILSIAKHKPV
VNQVECHPYL VQAELVSHCW SRNLTVTAYS PLGSPDRPWV TPGEALLLDD PRVVGIAKSY
NKTPAQVIIR WHIQRGVVCI PKSVTPSRIK QNIEVFDFKL SDEDMRLIES FNRNERFIIP
TVIKDGQKIW RDAKHPHFPF IEPY
